N-TERMINAL DOMAINS IN THE NR2 SUBUNIT CONTROL DESENSITIZATION OF NMDARECEPTORS

Recent molecular studies of glutamate channels have provided increasin gly detailed models of the agonist-binding site and of the channel por e. However, little information is available on the domains involved in channel gating. We examined the molecular determinants for the NR2-su bunit specificity of glycine-independent desensitization of NMDA chann els using NR2C/NR2A chimeric subunits expressed in HEK 293 cells. We s how that glycine-independent desensitization is controlled by N-termin al domains of the NR2 subunit that frank the putative agonist-binding domain: a four amino acid (aa) segment immediately preceding the first transmembrane domain (M1) and a region containing the leucine/isoleuc ine/valine-binding protein-like (LIVBP-like) domain. Our results provi de evidence for a functional role of the region containing the LIVBP-l ike domain in glutamate receptor channels. We suggest that the pre-M1 segment, presumably situated near the entrance to the pore, serves as a dynamic link between ligand binding and channel gating.